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NCT07189793

PHASE2

Toripalimab ± Sequential Intravesical Gemcitabine-Mitomycin C for BCG-Unresponsive/-Intolerant High-Risk NMIBC: Open-Label Randomized Phase 2 Study

Sponsor: First Affiliated Hospital of Wenzhou Medical University

View on ClinicalTrials.gov

Summary

This open-label, randomised, multicentre, phase 2 study (OHAI-NMIBC-01) compares toripalimab plus sequential intravesical gemcitabine followed by mitomycin C (GEM→MMC) with toripalimab alone in adults with BCG-unresponsive or BCG-intolerant high-risk non-muscle-invasive bladder cancer (HR-NMIBC). Two prespecified cohorts are analysed: (1) CIS cohort (CIS with/without Ta/T1) and (2) non-CIS cohort (high-risk Ta/T1 without CIS). In the combination arm, intravesical GEM→MMC is given weekly for 6 weeks (induction) and, for patients without recurrence at the first tumour assessment (\~month 3), monthly maintenance continues up to 24 months or until progression/unacceptable toxicity; toripalimab IV every 3 weeks starts during the first intravesical cycle and continues up to 24 months or until progression/unacceptable toxicity. The monotherapy arm receives toripalimab IV every 3 weeks up to 24 months or until progression/unacceptable toxicity. Cystoscopy and urine cytology are performed every 3 months; imaging every 24 weeks. Primary endpoints are 3-month complete response (CR) rate in the CIS cohort and median recurrence-free survival (RFS) in the non-CIS cohort. Secondary endpoints include landmark CR, PFS and OS, RFS/HG-RFS landmarks in the non-CIS cohort, and safety (CTCAE v5.0). Exploratory analyses will assess outcomes by protocol-defined PD-L1 status. Approximately 106 participants will be enrolled at multiple sites in China.

Official title: Toripalimab With Sequential Intravesical Gemcitabine-Mitomycin C Versus Toripalimab Alone for the Treatment of BCG-Unresponsive/-Intolerant High-Risk Non-Muscle-Invasive Bladder Cancer: An Open-Label, Randomized, Multicenter, Phase 2 Study

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

106

Start Date

2025-10

Completion Date

2028-10

Last Updated

2025-09-24

Healthy Volunteers

Conditions

Urinary Bladder Neoplasms Carcinoma, Transitional Cell Carcinoma in Situ of Bladder Non-Muscle-Invasive Bladder Cancer

Interventions

DRUG

Toripalimab

PD-1 inhibitor administered intravenously every 3 weeks (Q3W) for up to 24 months. Starts during the first intravesical treatment cycle.

DRUG

Gemcitabine (GEM)

Intravesical instillation as part of a sequential regimen with mitomycin C: weekly for 6 weeks (induction); if no recurrence at first tumour assessment (\~month 3), maintenance instillations continue monthly up to 24 months.

DRUG

Mitomycin C (MMC)

Intravesical instillation immediately after intravesical gemcitabine in the same visit (sequential regimen): weekly for 6 weeks (induction); if eligible, monthly maintenance up to 24 months.

Inclusion Criteria: 1. Age ≥18 years; sex: all; signed written informed consent by the participant or legally authorised representative. 2. Histologically confirmed high-risk non-muscle-invasive bladder cancer (HR-NMIBC), defined as any T1, high-grade Ta, and/or carcinoma in situ (CIS). 3. BCG-intolerant (unable to continue BCG because of severe adverse reactions) or meeting at least one definition of BCG treatment failure: 1. Persistent or recurrent CIS within 12 months after completion of adequate BCG (with or without concomitant NMIBC); 2. Recurrent high-grade Ta/T1 within 6 months after completion of adequate BCG; 3. High-grade T1 at the first evaluation after BCG induction (\~3 months); 4. Ta high-grade and/or CIS present or recurrent at \~3 months after receiving ≥5 BCG instillations. Adequate BCG, for the purposes of this protocol, is defined as receipt of at least 5 of 6 induction instillations (maintenance not required). 4. ECOG performance status 0-2. 5. Adequate organ function per protocol laboratory criteria. 6. No intravesical chemotherapy or immunotherapy between the most recent cystoscopy/TURBT and study start; a single immediate postoperative intravesical chemotherapy at the time of the most recent cystoscopy/TURBT is allowed during screening per local practice. 7. Willing and able to comply with study procedures. Exclusion Criteria: 1. Muscle-invasive bladder cancer (T2-T4). 2. Low-grade (LG) recurrence during or after BCG therapy. 3. Concomitant upper tract urothelial carcinoma, or lymph-node/distant metastasis. 4. Indwelling ureteral stent or known vesicoureteral reflux. 5. Contraindications to intravesical instillation, including within 2 weeks after TURBT, bladder perforation, symptomatic urinary tract infection, or gross haematuria. 6. Known hypersensitivity or contraindication to gemcitabine, mitomycin C, or toripalimab. 7. Systemic chemotherapy, small-molecule targeted therapy, or radiotherapy within 2 weeks before first study treatment. 8. Prior immune checkpoint inhibitor therapy. 9. Pregnant, planning pregnancy, or breastfeeding women. 10. Ongoing acute or chronic systemic infection, or history of active tuberculosis. 11. Other malignancy requiring active treatment. 12. Any condition that, in the investigator's judgment, makes participation not in the patient's best interest or could confound study results. Study Population Adults with BCG-unresponsive or BCG-intolerant HR-NMIBC treated at participating centres in China.

Locations (1)

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Clinical Research Directory

Toripalimab ± Sequential Intravesical Gemcitabine-Mitomycin C for BCG-Unresponsive/-Intolerant High-Risk NMIBC: Open-Label Randomized Phase 2 Study

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (1)